Subjects will be monitored for treatment-emergent and dose-limiting toxicity (DLT). If there are any adverse events (changes from baseline in laboratory parameters, vitals and/or infusion reactions) during these monitoring periods, the Independent Safety Committee, will discuss the dosing of the remaining subjects.

Before proceeding to the next dose cohort, the Independent Safety Committee will evaluate whether dose escalation will be permitted based on demonstration of adequate safety and tolerability.

A maximum of 56 healthy adult (male and female) subjects will participate in this study, in two stages. In Stage 1, the Single-Ascending Dose (SAD) phase of the study will have up to six cohorts with 4 subjects (3 receiving TKM-100201 and 1 receiving saline placebo) in each cohort. Additional cohorts may be enrolled if a maximum tolerated dose (MTD) is not established after the initial six cohorts. In Stage 2, the Multiple-Ascending Dose (MAD) portion of the study will have up to three cohorts with four subjects (3 receiving TKM-100201 and 1 receiving saline placebo) in each cohort. Additional cohorts may be enrolled if a maximum tolerated dose (MTD) is not established after the initial three cohorts.

Eligibility

Ages Eligible for Study:

18 Years to 50 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

Informed of the nature of the study and have agreed to and are able to read, review and sign the informed consent document at screening. The informed consent document will be written in English, therefore the volunteer must have the ability to read and communicate in English.

Able to comply with all protocol-specified visit schedules and requirements.

Completed the screening process within 14 days prior to dosing.

Healthy male and female volunteers 18 to 50 years of age, inclusive, at the time of dosing.

Judged by an Investigator to be in good health as documented by the medical history, physical examination (including but may not be limited to an evaluation of the cardiovascular, gastrointestinal, respiratory and central nervous systems), vital sign assessments, 12-lead ECG, clinical laboratory assessments, and by general observations. Any abnormalities or deviations outside the normal ranges for any of clinical testing (laboratory tests, ECG, vital signs) can be repeated at the discretion of the Investigator(s) and judged to be not clinically significant for study participation.

naturally postmenopausal (no menses) for > 2 years and has a documented FSH level >40 mIU/mL; or

have a documented history of ovarian failure; or

surgically postmenopausal (bilateral oophorectomy or hysterectomy). Female volunteers that are surgically postmenopausal must provide documentation of the bilateral oophorectomy or hysterectomy prior to Day 1 dosing to be eligible for participation in the study; or

Women of childbearing potential (FSH ≤40 mIU/mL) must have negative serum hCG at screening, a negative urine pregnancy test prior to the first study treatment, and must agree to utilize highly effective contraception methods (two separate forms of contraception, one of which must be an effective barrier method, or be non-heterosexually active, or have a vasectomized partner) from screening throughout the duration of study treatment and for 1 month after the last administration of investigational product.

Male volunteers who are sexually active must be willing to use effective barrier contraception (e.g., condom with spermicide) during heterosexual intercourse from screening throughout the duration of study treatment and for 1 month after the last dose of investigational product.

Exclusion Criteria:

Evidence or history of clinically significant hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic or allergic disease at screening or medication for comorbidity which, in dialogue between the Investigator and Medical Monitor would preclude subject participation in the clinical trial.

Reports an uncontrolled psychiatric disorder or neurologic disease or seizure disorder not controlled by medication.

Reports infections requiring antibiotic therapy within 30 days of screening (as determined by the Investigator[s]).

Reports a history of Ebola virus exposure.

Reports an occupational health risk of exposure to Ebola virus known to be higher than that of the general population.

Reports a known or suspected hypersensitivity or previous severe reactions to any of the constituents of the investigational product including oligonucleotide- or lipid-based products, liposomal drug products, and phospholipid-based products (parenteral nutrition, Intralipid).

Reports a history of clinically significant allergies including food or drug allergies.

Demonstrates a positive drug or alcohol screen.

Reports a history of drug or alcohol addiction or abuse within the past 1 year.

Reports donating blood within 28 days prior to dosing. All volunteers will be advised not to donate blood for four weeks after completing the study.

ports donating plasma (eg, plasmapheresis) within 14 days prior to dosing. All volunteers will be advised not to donate plasma for four weeks after completing the study.

Demonstrates, in the opinion of study staff, veins unsuitable for repeated venipuncture or IV infusion (eg, veins difficult to locate, access, or puncture; veins with a tendency to rupture during or after puncture).

Reports being capable of becoming pregnant, breastfeeding, or lactating.

Demonstrates a positive pregnancy screen.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01518881